Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17

Quirijn R.J.G. Tummers; Charlotte E.S. Hoogstins; Katja N. Gaarenstroom; Cor D. de Kroon; Mariette I.E. van Poelgeest; Jaap Vuyk; Tjalling Bosse; Vincent T.H.B.M. Smit; Cornelis J.H. van de Velde; Adam F. Cohen; Philip S. Low; Jacobus Burggraaf; Alexander L. Vahrmeijer

doi:10.18632/oncotarget.8282

Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17

Quirijn R.J.G. Tummers, Charlotte E.S. Hoogstins, Katja N. Gaarenstroom, Cor D. de Kroon, Mariette I.E. van Poelgeest, Jaap Vuyk, Tjalling Bosse, Vincent T.H.B.M. Smit, Cornelis J.H. van de Velde, Adam F. Cohen, Philip S. Low, Jacobus Burggraaf, Alexander L. Vahrmeijer

Research output: Contribution to journal › Article › peer-review

137 Scopus citations

Abstract

Introduction: Intraoperative fluorescence imaging of the folate-receptor alpha (FRα) could support completeness of resection in cancer surgery. Feasibility of EC17, a FRα-targeting agent that fluoresces at 500nm, was demonstrated in a limited series of ovarian cancer patients. Our objective was to evaluate EC17 in a larger group of ovarian cancer patients. In addition, we assessed the feasibility of EC17 in patients with breast cancer. Methods: Two-to-three hours before surgery 0.1mg/kg EC17 was intravenously administered to 12 patients undergoing surgery for ovarian cancer and to 3 patients undergoing surgery for biopsy-proven FRα-positive breast cancer. The number of lesions/positive margins detected with fluorescence and concordance between fluorescence and tumor- and FRα-status was assessed in addition to safety and pharmacokinetics. Results: Fluorescence imaging in ovarian cancer patients allowed detection of 57 lesions of which 44 (77%) appeared malignant on histopathology. Seven out of these 44 (16%) were not detected with inspection/palpation. Histopathology demonstrated concordance between fluorescence and FRα- and tumor status. Fluorescence imaging in breast cancer patients, allowed detection of tumor-specific fluorescence signal. At the 500nm wavelength, autofluorescence of normal breast tissue was present to such extent that it interfered with tumor identification. Conclusions: FRα is a favorable target for fluorescence-guided surgery as EC17 produced a clear fluorescent signal in ovarian and breast cancer tissue. This resulted in resection of ovarian cancer lesions that were otherwise not detected. Notwithstanding, autofluorescence caused false-positive lesions in ovarian cancer and difficulty in discriminating breast cancer-specific fluorescence from background signal. Optimization of the 500nm fluorophore, will minimize autofluorescence and further improve intraoperative tumor detection.

Original language	English (US)
Pages (from-to)	32144-32155
Number of pages	12
Journal	Oncotarget
Volume	7
Issue number	22
DOIs	https://doi.org/10.18632/oncotarget.8282
State	Published - May 31 2016

Keywords

Breast cancer
Fluorescence
Folate-receptor alpha
Image-guided surgery
Ovarian cancer

ASJC Scopus subject areas

Oncology

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10.18632/oncotarget.8282

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Tummers, Q. R. J. G., Hoogstins, C. E. S., Gaarenstroom, K. N., de Kroon, C. D., van Poelgeest, M. I. E., Vuyk, J., Bosse, T., Smit, V. T. H. B. M., van de Velde, C. J. H., Cohen, A. F., Low, P. S., Burggraaf, J., & Vahrmeijer, A. L. (2016). Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17. Oncotarget, 7(22), 32144-32155. https://doi.org/10.18632/oncotarget.8282

Tummers, QRJG, Hoogstins, CES, Gaarenstroom, KN, de Kroon, CD, van Poelgeest, MIE, Vuyk, J, Bosse, T, Smit, VTHBM, van de Velde, CJH, Cohen, AF, Low, PS, Burggraaf, J & Vahrmeijer, AL 2016, 'Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17', Oncotarget, vol. 7, no. 22, pp. 32144-32155. https://doi.org/10.18632/oncotarget.8282

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title = "Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17",

abstract = "Introduction: Intraoperative fluorescence imaging of the folate-receptor alpha (FRα) could support completeness of resection in cancer surgery. Feasibility of EC17, a FRα-targeting agent that fluoresces at 500nm, was demonstrated in a limited series of ovarian cancer patients. Our objective was to evaluate EC17 in a larger group of ovarian cancer patients. In addition, we assessed the feasibility of EC17 in patients with breast cancer. Methods: Two-to-three hours before surgery 0.1mg/kg EC17 was intravenously administered to 12 patients undergoing surgery for ovarian cancer and to 3 patients undergoing surgery for biopsy-proven FRα-positive breast cancer. The number of lesions/positive margins detected with fluorescence and concordance between fluorescence and tumor- and FRα-status was assessed in addition to safety and pharmacokinetics. Results: Fluorescence imaging in ovarian cancer patients allowed detection of 57 lesions of which 44 (77\%) appeared malignant on histopathology. Seven out of these 44 (16\%) were not detected with inspection/palpation. Histopathology demonstrated concordance between fluorescence and FRα- and tumor status. Fluorescence imaging in breast cancer patients, allowed detection of tumor-specific fluorescence signal. At the 500nm wavelength, autofluorescence of normal breast tissue was present to such extent that it interfered with tumor identification. Conclusions: FRα is a favorable target for fluorescence-guided surgery as EC17 produced a clear fluorescent signal in ovarian and breast cancer tissue. This resulted in resection of ovarian cancer lesions that were otherwise not detected. Notwithstanding, autofluorescence caused false-positive lesions in ovarian cancer and difficulty in discriminating breast cancer-specific fluorescence from background signal. Optimization of the 500nm fluorophore, will minimize autofluorescence and further improve intraoperative tumor detection.",

keywords = "Breast cancer, Fluorescence, Folate-receptor alpha, Image-guided surgery, Ovarian cancer",

author = "Tummers, \{Quirijn R.J.G.\} and Hoogstins, \{Charlotte E.S.\} and Gaarenstroom, \{Katja N.\} and \{de Kroon\}, \{Cor D.\} and \{van Poelgeest\}, \{Mariette I.E.\} and Jaap Vuyk and Tjalling Bosse and Smit, \{Vincent T.H.B.M.\} and \{van de Velde\}, \{Cornelis J.H.\} and Cohen, \{Adam F.\} and Low, \{Philip S.\} and Jacobus Burggraaf and Vahrmeijer, \{Alexander L.\}",

year = "2016",

month = may,

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doi = "10.18632/oncotarget.8282",

language = "English (US)",

volume = "7",

pages = "32144--32155",

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T1 - Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17

AU - Tummers, Quirijn R.J.G.

AU - Hoogstins, Charlotte E.S.

AU - Gaarenstroom, Katja N.

AU - de Kroon, Cor D.

AU - van Poelgeest, Mariette I.E.

AU - Vuyk, Jaap

AU - Bosse, Tjalling

AU - Smit, Vincent T.H.B.M.

AU - van de Velde, Cornelis J.H.

AU - Cohen, Adam F.

AU - Low, Philip S.

AU - Burggraaf, Jacobus

AU - Vahrmeijer, Alexander L.

PY - 2016/5/31

Y1 - 2016/5/31

N2 - Introduction: Intraoperative fluorescence imaging of the folate-receptor alpha (FRα) could support completeness of resection in cancer surgery. Feasibility of EC17, a FRα-targeting agent that fluoresces at 500nm, was demonstrated in a limited series of ovarian cancer patients. Our objective was to evaluate EC17 in a larger group of ovarian cancer patients. In addition, we assessed the feasibility of EC17 in patients with breast cancer. Methods: Two-to-three hours before surgery 0.1mg/kg EC17 was intravenously administered to 12 patients undergoing surgery for ovarian cancer and to 3 patients undergoing surgery for biopsy-proven FRα-positive breast cancer. The number of lesions/positive margins detected with fluorescence and concordance between fluorescence and tumor- and FRα-status was assessed in addition to safety and pharmacokinetics. Results: Fluorescence imaging in ovarian cancer patients allowed detection of 57 lesions of which 44 (77%) appeared malignant on histopathology. Seven out of these 44 (16%) were not detected with inspection/palpation. Histopathology demonstrated concordance between fluorescence and FRα- and tumor status. Fluorescence imaging in breast cancer patients, allowed detection of tumor-specific fluorescence signal. At the 500nm wavelength, autofluorescence of normal breast tissue was present to such extent that it interfered with tumor identification. Conclusions: FRα is a favorable target for fluorescence-guided surgery as EC17 produced a clear fluorescent signal in ovarian and breast cancer tissue. This resulted in resection of ovarian cancer lesions that were otherwise not detected. Notwithstanding, autofluorescence caused false-positive lesions in ovarian cancer and difficulty in discriminating breast cancer-specific fluorescence from background signal. Optimization of the 500nm fluorophore, will minimize autofluorescence and further improve intraoperative tumor detection.

AB - Introduction: Intraoperative fluorescence imaging of the folate-receptor alpha (FRα) could support completeness of resection in cancer surgery. Feasibility of EC17, a FRα-targeting agent that fluoresces at 500nm, was demonstrated in a limited series of ovarian cancer patients. Our objective was to evaluate EC17 in a larger group of ovarian cancer patients. In addition, we assessed the feasibility of EC17 in patients with breast cancer. Methods: Two-to-three hours before surgery 0.1mg/kg EC17 was intravenously administered to 12 patients undergoing surgery for ovarian cancer and to 3 patients undergoing surgery for biopsy-proven FRα-positive breast cancer. The number of lesions/positive margins detected with fluorescence and concordance between fluorescence and tumor- and FRα-status was assessed in addition to safety and pharmacokinetics. Results: Fluorescence imaging in ovarian cancer patients allowed detection of 57 lesions of which 44 (77%) appeared malignant on histopathology. Seven out of these 44 (16%) were not detected with inspection/palpation. Histopathology demonstrated concordance between fluorescence and FRα- and tumor status. Fluorescence imaging in breast cancer patients, allowed detection of tumor-specific fluorescence signal. At the 500nm wavelength, autofluorescence of normal breast tissue was present to such extent that it interfered with tumor identification. Conclusions: FRα is a favorable target for fluorescence-guided surgery as EC17 produced a clear fluorescent signal in ovarian and breast cancer tissue. This resulted in resection of ovarian cancer lesions that were otherwise not detected. Notwithstanding, autofluorescence caused false-positive lesions in ovarian cancer and difficulty in discriminating breast cancer-specific fluorescence from background signal. Optimization of the 500nm fluorophore, will minimize autofluorescence and further improve intraoperative tumor detection.

KW - Breast cancer

KW - Fluorescence

KW - Folate-receptor alpha

KW - Image-guided surgery

KW - Ovarian cancer

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JO - Oncotarget

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Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17

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